Study reveals how the immune response is alerted in fruitflies

Mammals and fruitflies (otherwise known as Drosophila) face very different natural pathogens yet their immune systems resemble each other in many ways.

Lecturer Dr Petros Ligoxygakis and colleagues in his lab and in France and Germany, have recently identified a mechanism which is key to providing immune defence in the larvae of Drosophila and which parallels the mammalian immune response1.

The finding illustrates the value of using Drosophila as a model system for unraveling the complexities of the human immune system.

Drosophila larvae are transparent and so offer a unique opportunity to follow the molecular events that are triggered by infection. The immune system in larvae marshals two lines of defence when it is invaded by a pathogen.

The fat body, an organ similar to the mammalian liver, releases a burst of potent substances called anti-microbial peptides (AMP). Complementing this, the blood cell-like haemocytes circulating round the larvae engulf the invading micro-organism in the same way that mammalian macrophages do.

In mammals, infection stimulates a similar two-pronged attack. But the stimulation of macrophages also triggers the release of cytokines - molecular signals which remotely activate a cell or tissue and recruit it in the fight against infection.

"No association between the antimicrobial peptide response and blood cells has been previously identified in Drosophila," Dr Ligoxygakis explains. "We were trying to see whether there is a parallel to what happens in mammals where you have cytokines that are secreted by macrophages."

A Drosophila larva in which the haemocytes have been marked with a green flourescent tag. An arrow points to the organ which makes these cells

Through a series of experiments including targeted ablation of the haemocytes in larvae, the group found that haemocytes release a signal that is required for a normal immune response. That signal is a cytokine-like molecule called Spätzle, which is necessary and sufficient for production of AMP in the fat body.

However, the link between haemocytes and AMP release in the fat body is absent in the adult Drosophila. Dr Ligoxygakis believes that there could be a number of explanations for this. For example, the immune systems of adults and larvae may be adapted to the different range of immunological threats each faces.

"There are a lot of physiological differences between this larval stage and adults, and there are differences in the way they live. Fruitflies in the wild grow on decomposing material. Larvae are always immersed in this media and this is an extremely dangerous environment."

Spätzle triggers the fat body in response to infections from fungi and a class of bacteria known as Gram-positive. Dr Ligoxygakis will be looking to see whether other cytokines may be alerting the fat body to infections from different microbes such as Gram-negative bacteria.